The primary goal of this program project is to determine the properties of vascular smooth muscle (VSM) that regulate its contractile state, and hence blood flow, under physiological conditions and subsequently in hypertension. Since numerous factors may play a role in altering VSM contractility, and since so little is known about this important tissue, a multifaceted study has been undertaken involving 11 faculty members who represent the Departments of Biochemistry, Pharmacology and Physiology. The 7 projects deal with the metabolism of VSM ("Energy metabolism and protein turnover in VSM", "VSM response to serum lipoproteins", "Vasoactive metabolites from VSM and parenchymal tissue", "Cyclic nucleotide metabolism in smooth muscle cultures"), the mechanics of VSM ("The contractile system of VSM") and "The electrophysiology of VSM". The various projects are closely related so that there is considerable interaction among the participants. The experiments include whole animal studies, isolated tissues and organs, VSM cell cultures and subcellular fractions, and core facilities are provided to meet the experimental needs of the investigators. An electron microscope core facility was already present in the Physiology Department and a second core facility for spontaneously hypertensive rats and suitable controls has been established. A third core facility that serves that project is a VSM cell culture core which supplies materials for all of the participants. The information to be gained from this program project will not only provide necessary basic data on the mechanisms involved in the function of VSM but may well lead to more rational approaches for the treatment of disease caused by abnormally functioning VSM.